Paul Jibon Kumar, Azmal Mahir, Alam Tasnim, Talukder Omar Faruk, Ghosh Ajit
Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, Bangladesh.
PLoS Negl Trop Dis. 2025 Mar 18;19(3):e0012914. doi: 10.1371/journal.pntd.0012914. eCollection 2025 Mar.
Dengue fever, caused by the dengue virus (DENV), presents a significant global health concern, with millions of cases reported annually. Despite significant progress in understanding Dengue fever, effective prognosis and treatment remain elusive due to the complex clinical presentations and limitations in current diagnostic methods. The virus, transmitted primarily by the Aedes aegypti mosquito, exists in four closely related forms, each capable of causing flu-like symptoms ranging from mild febrile illness to severe manifestations such as plasma leakage and hemorrhagic fever. Although advancements in diagnostic techniques have been made, early detection of severe dengue remains difficult due to the complexity of its clinical presentations. This study conducted a comprehensive analysis of differential gene expression in dengue fever patients using multiple microarray datasets from the NCBI GEO database. Through bioinformatics approaches, 163 potential biomarker genes were identified, with some overlapping previously reported biomarkers and others representing novel candidates. Notably, AURKA, BUB1, BUB1B, BUB3, CCNA2, CCNB2, CDC6, CDK1, CENPE, EXO1, NEK2, ZWINT, and STAT1 were among the most significant biomarkers. These genes are involved in critical cellular processes, such as cell cycle regulation and mitotic checkpoint control, which are essential for immune cell function and response. Functional enrichment analysis revealed that the dysregulated genes were predominantly associated with immune response to the virus, cell division, and RNA processing. Key regulatory genes such as AURKA, BUB1, BUB3, and CDK1 are found to be involved in cell cycle regulation and have roles in immune-related pathways, underscoring their importance in the host immune response to Dengue virus infection. This study provides novel insights into the molecular mechanisms underlying Dengue fever pathogenesis, highlighting key regulatory genes such as AURKA and CDK1 that could serve as potential biomarkers for early diagnosis and targets for therapeutic intervention, paving the way for improved management of the disease.
登革热由登革病毒(DENV)引起,是一个重大的全球健康问题,每年报告的病例数以百万计。尽管在理解登革热方面取得了重大进展,但由于临床表现复杂以及当前诊断方法存在局限性,有效的预后和治疗仍然难以实现。该病毒主要通过埃及伊蚊传播,有四种密切相关的形式,每种形式都能引起类似流感的症状,从轻度发热疾病到严重表现,如血浆渗漏和出血热。尽管诊断技术有所进步,但由于临床表现复杂,严重登革热的早期检测仍然困难。本研究使用来自NCBI GEO数据库的多个微阵列数据集,对登革热患者的差异基因表达进行了全面分析。通过生物信息学方法,鉴定出163个潜在的生物标志物基因,其中一些与先前报道的生物标志物重叠,另一些则代表新的候选基因。值得注意的是,极光激酶A(AURKA)、BUB1、BUB1B、BUB3、细胞周期蛋白A2(CCNA2)、细胞周期蛋白B2(CCNB2)、细胞分裂周期蛋白6(CDC6)、细胞周期蛋白依赖性激酶1(CDK1)、着丝粒蛋白E(CENPE)、核酸外切酶1(EXOI)、丝氨酸/苏氨酸蛋白激酶2(NEK2)、ZW10相互作用蛋白(ZWINT)和信号转导和转录激活因子1(STAT1)是最重要的生物标志物之一。这些基因参与关键的细胞过程,如细胞周期调控和有丝分裂检查点控制,这对免疫细胞功能和反应至关重要。功能富集分析表明,失调的基因主要与对病毒的免疫反应、细胞分裂和RNA加工有关。发现关键调控基因如AURKA、BUB1、BUB3和CDK1参与细胞周期调控,并在免疫相关途径中发挥作用,强调了它们在宿主对登革病毒感染的免疫反应中的重要性。本研究为登革热发病机制的分子机制提供了新的见解,突出了关键调控基因如AURKA和CDK1,它们可作为早期诊断的潜在生物标志物和治疗干预的靶点,为改善该疾病的管理铺平了道路。